背景：胃癌（GC）是最常见的恶性肿瘤之一，其5年生存率较低。然而，如果在早期诊断，可以通过内窥镜治疗进行治愈，并有良好的预后。虽然胃肠X线和上消化道内窥镜在一些高风险胃癌国家（如日本和韩国）被用作全国胃癌筛查方法，但其辐射暴露、侵入性和高昂的成本表明它们并非适用于许多国家的胃癌早期检测的最佳工具。因此，在临床环境中急需一种具有经济效益且高度准确的胃癌早期检测方法。DNA甲基化在癌症进展和转移中起着关键作用，并已被证明是癌症早期检测的有希望的标志物。目的和方法：本综述全面概述了与GC相关的DNA甲基化标志物的当前状况、GC早期检测研究开展的方法、甲基化标志物发现和应用的挑战以及利用甲基化标志物进行GC早期检测的未来前景。通过我们的分析，我们发现目前报告的与GC相关的DNA甲基化标志物主要处于早期发现阶段。它们大多仅在组织样本中进行了评估。基于血液的非侵入性检测方法大多缺乏标准化的采样方案、前分析程序和多中心验证，并且在早期GC检测中的敏感性不足。同时，报道的GC DNA甲基化标志物通常被认为是全癌标志物。结论：因此，未来的努力应重点确定与GC特异性的额外甲基化标志物，并建立依赖于这些标志物的非侵入性诊断方法。这些方法应经过多中心、大规模的前瞻性验证，针对多样化的人群进行验证。版权所有 © 2023 Xue, Huang, Pei, Wang and Dai.

Background: Gastric cancer (GC) is one of the most common malignancies, with a low 5-year survival rate. However, if diagnosed at an early stage, it can be cured by endoscopic treatment and has a good prognosis. While gastrointestinal X-ray and upper endoscopy are used as national GC screening methods in some GC high-risk countries, such as Japan and Korea, their radiation exposure, invasiveness, and high cost suggest that they are not the optimal tools for early detection of GC in many countries. Therefore, a cost-effective, and highly accurate method for GC early detection is urgently needed in clinical settings. DNA methylation plays a key role in cancer progression and metastasis and has been demonstrated as a promising marker for cancer early detection. Aims and methods: This review provides a comprehensive overview of the current status of DNA methylation markers associated with GC, the assays developed for GC early detection, challenges in methylation marker discovery and application, and the future prospects of utilizing methylation markers for early detection of GC. Through our analysis, we found that the currently reported DNA methylation markers related to GC are mainly in the early discovery stage. Most of them have only been evaluated in tissue samples. The majority of non-invasive assays developed based on blood lack standardized sampling protocols, pre-analytical procedures, and multicenter validation, and they exhibit insufficient sensitivity for early-stage GC detection. Meanwhile, the reported GC DNA methylation markers are generally considered pan-cancer markers. Conclusion: Therefore, future endeavors should focus on identifying additional methylation markers specific to GC and establishing non-invasive diagnostic assays that rely on these markers. These assays should undergo multicenter, large-scale prospective validation in diverse populations.Copyright © 2023 Xue, Huang, Pei, Wang and Dai.